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1.
J Biol Chem ; 300(8): 107556, 2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-39002683

RESUMO

Diversity, a hallmark of G protein-coupled receptor (GPCR) signaling, partly stems from alternative splicing of a single gene generating more than one isoform for a receptor. Additionally, receptor responses to ligands can be attenuated by desensitization upon prolonged or repeated ligand exposure. Both phenomena have been demonstrated and exemplified by the deuterostome tachykinin signaling system, although the role of phosphorylation in desensitization remains a subject of debate. Here, we describe the signaling system for tachykinin-related peptides (TKRPs) in a protostome, mollusk Aplysia. We cloned the Aplysia TKRP precursor, which encodes three TKRPs (apTKRP-1, apTKRP-2a, and apTKRP-2b) containing the FXGXR-amide motif. In situ hybridization and immunohistochemistry showed predominant expression of TKRP mRNA and peptide in the cerebral ganglia. TKRPs and their posttranslational modifications were observed in extracts of central nervous system ganglia using mass spectrometry. We identified two Aplysia TKRP receptors (apTKRPRs), named apTKRPR-A and apTKRPR-B. These receptors are two isoforms generated through alternative splicing of the same gene and differ only in their intracellular C termini. Structure-activity relationship analysis of apTKRP-2b revealed that both C-terminal amidation and conserved residues of the ligand are critical for receptor activation. C-terminal truncates and mutants of apTKRPRs suggested that there is a C-terminal phosphorylation-independent desensitization for both receptors. Moreover, apTKRPR-B also exhibits phosphorylation-dependent desensitization through the phosphorylation of C-terminal Ser/Thr residues. This comprehensive characterization of the Aplysia TKRP signaling system underscores the evolutionary conservation of the TKRP and TK signaling systems, while highlighting the intricacies of receptor regulation through alternative splicing and differential desensitization mechanisms.

2.
J Neurophysiol ; 130(4): 941-952, 2023 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-37671445

RESUMO

Command systems integrate sensory information and then activate the interneurons and motor neurons that mediate behavior. Much research has established that the higher-order projection neurons that constitute these systems can play a key role in specifying the nature of the motor activity induced, or determining its parametric features. To a large extent, these insights have been obtained by contrasting activity induced by stimulating one neuron (or set of neurons) to activity induced by stimulating a different neuron (or set of neurons). The focus of our work differs. We study one type of motor program, ingestive feeding in the mollusc Aplysia californica, which can either be triggered when a single projection neuron (CBI-2) is repeatedly stimulated or can be triggered by projection neuron coactivation (e.g., activation of CBI-2 and CBI-3). We ask why this might be an advantageous arrangement. The cellular/molecular mechanisms that configure motor activity are different in the two situations because the released neurotransmitters differ. We focus on an important consequence of this arrangement, the fact that a persistent state can be induced with repeated CBI-2 stimulation that is not necessarily induced by CBI-2/3 coactivation. We show that this difference can have consequences for the ability of the system to switch from one type of activity to another.NEW & NOTEWORTHY We study a type of motor program that can be induced either by stimulating a higher-order projection neuron that induces a persistent state, or by coactivating projection neurons that configure activity but do not produce a state change. We show that when an activity is configured without a state change, it is possible to immediately return to an intermediate state that subsequently can be converted to any type of motor program.


Assuntos
Aplysia , Comportamento Alimentar , Animais , Comportamento Alimentar/fisiologia , Aplysia/fisiologia , Ingestão de Alimentos/fisiologia , Interneurônios/fisiologia , Neurônios Motores/fisiologia , Gânglios dos Invertebrados/fisiologia
3.
J Neurosci ; 41(10): 2152-2163, 2021 03 10.
Artigo em Inglês | MEDLINE | ID: mdl-33500278

RESUMO

Modulators are generally expected to establish a network configuration that is appropriate for the current circumstances. We characterize a situation where the opposite is apparently observed. A network effect of a peptide modulator is counterproductive in that it tends to impede rather than promote the creation of the configuration that is appropriate when the modulator is released. This raises a question: why does release occur? We present data that strongly suggest that it impacts task switching. Our experiments were conducted in an Aplysia feeding network that generates egestive and ingestive motor programs. Initial experiments focused on egestive activity and the neuron B8. As activity becomes egestive, there is an increase in synaptic drive to B8 and its firing frequency increases (Wang et al., 2019). We show that, as this occurs, there is also a persistent current that develops in B8 that is outward rather than inward. Dynamic clamp introduction of this current decreases excitability. When there is an egestive-ingestive task switch in Aplysia, negative biasing is observed (i.e., a bout of egestive activity has a negative impact on a subsequent attempt to initiate an ingestive response) (Proekt et al., 2004). Using an in vitro analog of negative biasing, we demonstrate that the outward current that develops during egestive priming plays an important role in establishing this phenomenon. Our data suggest that, although the outward current induced as activity becomes egestive is counterproductive at the time, it plays an anticipatory role in that it subsequently impacts task switching.SIGNIFICANCE STATEMENT In this study, we identify a peptide-induced circuit modification (induction of an outward current) that does not immediately promote the establishment of a behaviorally appropriate network configuration. We ask why this might occur, and present data that strongly suggest that it plays an important role during task switching. Specifically, our data suggest that the outward current we characterize plays a role in the negative biasing that is seen in the mollusc Aplysia when there is a transition from egestive to ingestive activity. It is possible that the mechanism that we describe operates in other species. A negative effect of egestion on subsequent ingestion is observed throughout the animal kingdom.


Assuntos
Potenciais de Ação/fisiologia , Aplysia/fisiologia , Neurônios Motores/fisiologia , Animais , Comportamento Alimentar/fisiologia , Gânglios dos Invertebrados/fisiologia
4.
J Neurophysiol ; 127(6): 1445-1459, 2022 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-35507477

RESUMO

These experiments focus on an interneuron (B63) that is part of the feeding central pattern generator (CPG) in Aplysia californica. Previous work has established that B63 is critical for program initiation regardless of the type of evoked activity. B63 receives input from a number of different elements of the feeding circuit. Program initiation occurs reliably when some are activated, but we show that it does not occur reliably with activation of others. When program initiation is reliable, modulatory neuropeptides are released. For example, previous work has established that an ingestive input to the feeding CPG, cerebral buccal interneuron 2 (CBI-2), releases feeding circuit activating peptide (FCAP) and cerebral peptide 2 (CP-2). Afferents with processes in the esophageal nerve (EN) that trigger egestive motor programs release small cardioactive peptide (SCP). Previous studies have described divergent cellular and molecular effects of FCAP/CP-2 and SCP on the feeding circuit that specify motor activity. Here, we show that FCAP/CP-2 and SCP additionally increase the B63 excitability. Thus, we show that peptides that have well-characterized divergent effects on the feeding circuit additionally act convergently at the level of a single neuron. Since convergent effects of FCAP/CP-2 and SCP are not necessary for specifying the type of network output, we ask why they might be important. Our data suggest that they have an impact during a task switch, i.e., when there is a switch from egestive to ingestive activity.NEW & NOTEWORTHY The activity of multifunctional central pattern generators (CPGs) is often configured by neuromodulators that exert divergent effects that are necessary to specify motor output. We demonstrate that ingestive and egestive inputs to the feeding CPG in Aplysia act convergently (as well as divergently). We ask why this convergence may be important and suggest that it may be a mechanism for a type of arousal that occurs during task switching.


Assuntos
Geradores de Padrão Central , Neuropeptídeos , Animais , Aplysia/fisiologia , Comportamento Alimentar/fisiologia , Gânglios dos Invertebrados/fisiologia , Interneurônios/fisiologia , Neuropeptídeos/farmacologia
5.
J Neurosci ; 39(44): 8705-8716, 2019 10 30.
Artigo em Inglês | MEDLINE | ID: mdl-31548235

RESUMO

The characteristics of a network are determined by parameters that describe the intrinsic properties of the component neurons and their synapses. Degeneracy occurs when more than one set of parameters produces the same (or very similar) output. It is not clear whether network degeneracy impacts network function or is simply a reflection of the fact that, although it is important for a network to be able to generate a particular output, it is not important how this is achieved. We address this issue in the feeding network of the mollusc Aplysia In this system, there are two stimulation paradigms that generate egestive motor programs: repetition priming and positive biasing. We demonstrate that circuit parameters differ in the 2 cases (e.g., egestive repetition priming requires activity in an interneuron, B20, which is not essential for positive biasing). We show that degeneracy has consequences for task switching. If egestive repetition priming is immediately followed by stimulation of an ingestive input to the feeding central pattern generator, the first few cycles of activity are egestive (not ingestive). In this situation, there is a task switch cost. This "cost" is in part due to the potentiating effect of egestive repetition priming on B20. In contrast, there is no switch cost after positive biasing. Stimulation of the ingestive central pattern generator input immediately triggers ingestive activity. Our results indicate that the mechanisms used to pattern activity can impact network function in that they can determine how readily a network can switch from one configuration to another.SIGNIFICANCE STATEMENT A particular pattern of neural activity can be generated by more than one set of circuit parameters. How or whether this impacts network function is unclear. We address this issue in the feeding network of Aplysia and demonstrate that degeneracy in network function can have consequences for task switching. Namely, we show that, when egestive activity is generated via one set of circuit modifications, an immediate switch to ingestive activity is not possible. In contrast, rapid transitions to ingestive activity are possible if egestive activity is generated via a different set of circuit modifications.


Assuntos
Ingestão de Alimentos/fisiologia , Comportamento Alimentar/fisiologia , Neurônios/fisiologia , Priming de Repetição/fisiologia , Potenciais de Ação , Animais , Aplysia , Gânglios dos Invertebrados/fisiologia , Atividade Motora , Vias Neurais/fisiologia
6.
J Neurosci ; 38(29): 6475-6490, 2018 07 18.
Artigo em Inglês | MEDLINE | ID: mdl-29934354

RESUMO

Many neural networks are multitasking and receive modulatory input, which configures activity. As a result, these networks can enter a relatively persistent state in which they are biased to generate one type of output as opposed to another. A question we address is as follows: what happens to this type of state when the network is forced to task-switch? We address this question in the feeding system of the mollusc Aplysia This network generates ingestive and egestive motor programs. We focus on an identified neuron that is selectively active when programs are ingestive. Previous work has established that the increase in firing frequency observed during ingestive programs is at least partially mediated by an excitability increase. Here we identify the underlying cellular mechanism as the induction of a cAMP-dependent inward current. We ask how this current is impacted by the subsequent induction of egestive activity. Interestingly, we demonstrate that this task-switch does not eliminate the inward current but instead activates an outward current. The induction of the outward current obviously reduces the net inward current in the cell. This produces the decrease in excitability and firing frequency required for the task-switch. Importantly, however, the persistence of the inward current is not impacted. It remains present and coexists with the outward current. Consequently, when effects of egestive priming and the outward current dissipate, firing frequency and excitability remain above baseline levels. This presumably has important functional implications in that it will facilitate a return to ingestive activity.SIGNIFICANCE STATEMENT Under physiological conditions, an animal generating a particular type of motor activity can be forced to at least briefly task-switch. In some circumstances, this involves the temporary induction of an "antagonistic" or incompatible motor program. For example, ingestion can be interrupted by a brief period of egestive activity. In this type of situation, it is often desirable for behavioral switching to occur rapidly and efficiently. In this report, we focus on a particular aspect of this type of task-switch. We determine how the priming that occurs when a multitasking network repeatedly generates one type of motor activity can be retained during the execution of an incompatible motor program.


Assuntos
Comportamento Alimentar/fisiologia , Neurônios/fisiologia , Priming de Repetição/fisiologia , Potenciais de Ação/fisiologia , Animais , Aplysia , Gânglios dos Invertebrados/fisiologia , Atividade Motora/fisiologia , Rede Nervosa
7.
J Biol Chem ; 292(46): 18775-18789, 2017 11 17.
Artigo em Inglês | MEDLINE | ID: mdl-28924050

RESUMO

A better understanding of neuromodulation in a behavioral system requires identification of active modulatory transmitters. Here, we used identifiable neurons in a neurobiological model system, the mollusc Aplysia, to study neuropeptides, a diverse class of neuromodulators. We took advantage of two types of feeding neurons, B48 and B1/B2, in the Aplysia buccal ganglion that might contain different neuropeptides. We performed a representational difference analysis (RDA) by subtraction of mRNAs in B48 versus mRNAs in B1/B2. The RDA identified an unusually long (2025 amino acids) peptide precursor encoding Aplysia leucokinin-like peptides (ALKs; e.g. ALK-1 and ALK-2). Northern blot analysis revealed that, compared with other ganglia (e.g. the pedal-pleural ganglion), ALK mRNA is predominantly present in the buccal ganglion, which controls feeding behavior. We then used in situ hybridization and immunohistochemistry to localize ALKs to specific neurons, including B48. MALDI-TOF MS on single buccal neurons revealed expression of 40 ALK precursor-derived peptides. Among these, ALK-1 and ALK-2 are active in the feeding network; they shortened the radula protraction phase of feeding motor programs triggered by a command-like neuron. We also found that this effect may be mediated by the ALK-stimulated enhancement of activity of an interneuron, which has previously been shown to terminate protraction. We conclude that our multipronged approach is effective for determining the structure and defining the diverse functions of leucokinin-like peptides. Notably, the ALK precursor is the first verified nonarthropod precursor for leucokinin-like peptides with a novel, marked modulatory effect on a specific parameter (protraction duration) of feeding motor programs.


Assuntos
Aplysia/fisiologia , Gânglios dos Invertebrados/fisiologia , Neuropeptídeos/metabolismo , Animais , Aplysia/química , Aplysia/citologia , Aplysia/genética , Comportamento Alimentar , Gânglios dos Invertebrados/química , Gânglios dos Invertebrados/metabolismo , Neurônios/química , Neurônios/citologia , Neurônios/metabolismo , Neuropeptídeos/análise , Neuropeptídeos/genética , Processamento de Proteína Pós-Traducional , RNA Mensageiro/análise , RNA Mensageiro/genética , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz
8.
J Neurophysiol ; 118(3): 1861-1870, 2017 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-28679841

RESUMO

Many central pattern generator (CPG)-mediated behaviors are episodic, meaning that they are not continuously ongoing; instead, there are pauses between bouts of activity. This raises an interesting possibility, that the neural networks that mediate these behaviors are not operating under "steady-state" conditions; i.e., there could be dynamic changes in motor activity as it stops and starts. Research in the feeding system of the mollusk Aplysia californica has demonstrated that this can be the case. After a pause, initial food grasping responses are relatively weak. With repetition, however, responses strengthen. In this review we describe experiments that have characterized cellular/molecular mechanisms that produce these changes in motor activity. In particular, we focus on cumulative effects of modulatory neuropeptides. Furthermore, we relate Aplysia research to work in other systems and species, and develop a hypothesis that postulates that changes in response magnitude are a reflection of an efficient feeding strategy.


Assuntos
Aplysia/fisiologia , Geradores de Padrão Central/fisiologia , Comportamento Alimentar , Priming de Repetição , Animais , Movimento
9.
J Neurophysiol ; 117(6): 2104-2112, 2017 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-28275057

RESUMO

In a type of short-term plasticity that is observed in a number of systems, synaptic transmission is potentiated by depolarizing changes in the membrane potential of the presynaptic neuron before spike initiation. This digital-analog form of plasticity is graded. The more depolarized the neuron, the greater the increase in the efficacy of synaptic transmission. In a number of systems, including the system presently under investigation, this type of modulation is calcium dependent, and its graded nature is presumably a consequence of a direct relationship between the intracellular calcium concentration ([Ca2+]i) and the effect on synaptic transmission. It is therefore of interest to identify factors that determine the magnitude of this type of calcium signal. We studied a synapse in Aplysia and demonstrate that there can be a contribution from currents activated during spiking. When neurons spike, there are localized increases in [Ca2+]i that directly trigger neurotransmitter release. Additionally, spiking can lead to global increases in [Ca2+]i that are reminiscent of those induced by subthreshold depolarization. We demonstrate that these spike-induced increases in [Ca2+]i result from the activation of a current not activated by subthreshold depolarization. Importantly, they decay with a relatively slow time constant. Consequently, with repeated spiking, even at a low frequency, they readily summate to become larger than increases in [Ca2+]i induced by subthreshold depolarization alone. When this occurs, global increases in [Ca2+]i induced by spiking play the predominant role in determining the efficacy of synaptic transmission.NEW & NOTEWORTHY We demonstrate that spiking can induce global increases in the intracellular calcium concentration ([Ca2+]i) that decay with a relatively long time constant. Consequently, summation of the calcium signal occurs even at low firing frequencies. As a result there is significant, persistent potentiation of synaptic transmission.


Assuntos
Cálcio/metabolismo , Espaço Intracelular/metabolismo , Plasticidade Neuronal/fisiologia , Sinapses/metabolismo , Transmissão Sináptica/fisiologia , Análise de Variância , Animais , Aplysia , Cátions Bivalentes/metabolismo , Feminino , Gânglios dos Invertebrados/citologia , Gânglios dos Invertebrados/metabolismo , Masculino , Mecanorreceptores/citologia , Mecanorreceptores/metabolismo , Microeletrodos , Técnicas de Cultura de Tecidos , Imagens com Corantes Sensíveis à Voltagem
10.
Sheng Li Xue Bao ; 69(4): 461-466, 2017 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-28825105

RESUMO

Improvements in the imaging of neural circuits are essential for studies of network function in both invertebrates and vertebrates. Therefore, CLARITY, a new imaging enhancement technique developed for mouse brains has attracted broad interest from researchers working on other species. We studied the potential of a modified version of CLARITY to enhance the imaging of ganglia in an invertebrate Aplysia. For example, we have modified the hydrogel solution and designed a small container for the Aplysia ganglia. The ganglia were first processed for immunohistochemistry, and then for CLARITY. We examined the compatibility of these techniques and the extent to which the imaging of fluorescence improved using confocal microscopy. We found that CLARITY did indeed enhance the imaging of CP2 immunopositive neurons in Aplysia ganglia. For example, it improved visualization of small, weak immunoreactive neurons deep in the ganglia. Our modifications of CLARITY make this new method suitable for future use in Aplysia experiments. Furthermore, our techniques are likely to facilitate imaging in other invertebrate ganglia.


Assuntos
Aplysia/anatomia & histologia , Gânglios dos Invertebrados/diagnóstico por imagem , Aumento da Imagem/métodos , Animais , Imuno-Histoquímica , Neurônios/citologia
11.
J Neurosci ; 35(16): 6326-34, 2015 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-25904786

RESUMO

We investigate stimulus specificity of repetition priming in a tractable model system; the feeding network of Aplysia. Previous studies primarily focused on an aspect of behavior that is altered during ingestive priming, radula opening. Priming of radula opening occurs when two modulatory peptides [feeding circuit activating peptide (FCAP) and cerebral peptide-2 (CP-2)] are released from the cholinergic command-like neuron cerebral buccal interneuron 2. Effects of FCAP/CP-2 on radula opening motor neurons are cAMP mediated. The present experiments sought to determine whether FCAP/CP-2 and cAMP are also involved in the priming of radula opening during an incompatible activity, i.e., during egestive motor programs. Egestive priming is induced when motor programs are triggered by afferents with processes in the esophageal nerve. We demonstrate that egestive priming is not FCAP/CP-2 mediated. Instead, it is induced by an unrelated peptide (small cardioactive peptide), which exerts PKC-mediated effects. Our data, therefore, suggest that different feeding motor programs are primed via actions of different sets of intercellular and intracellular substances. We suggest that this accounts for the stimulus specificity that can be characteristic of repetition priming. Different stimuli activate different central pattern generator inputs. These inputs release different modulators, which induce functionally distinct motor programs.


Assuntos
Neuropeptídeos/fisiologia , Priming de Repetição/fisiologia , Transmissão Sináptica/fisiologia , Animais , Aplysia , Comportamento Alimentar/fisiologia
12.
J Neurosci ; 35(24): 9137-49, 2015 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-26085636

RESUMO

Understanding circuit function requires the characterization of component neurons and their neurotransmitters. Previous work on radula protraction in the Aplysia feeding circuit demonstrated that critical neurons initiate feeding via cholinergic excitation. In contrast, it is less clear how retraction is mediated at the interneuronal level. In particular, glutamate involvement was suggested, but was not directly confirmed. Here we study a suspected glutamatergic retraction interneuron, B64. We used the representational difference analysis (RDA) method to successfully clone an Aplysia vesicular glutamate transporter (ApVGLUT) from B64 and from a glutamatergic motor neuron B38. Previously, RDA was used to characterize novel neuropeptides. Here we demonstrate its utility for characterizing other types of molecules. Bioinformatics suggests that ApVGLUT is more closely related to mammalian VGLUTs than to Drosophila and Caenorhabditis elegans VGLUTs. We expressed ApVGLUT in a cell line, and demonstrated that it indeed transports glutamate in an ATP and proton gradient-dependent manner. We mapped the ApVGLUT distribution in the CNS using in situ hybridization and immunocytochemistry. Further, we demonstrated that B64 is ApVGLUT positive, supporting the idea that it is glutamatergic. Although glutamate is primarily an excitatory transmitter in the mammalian CNS, B64 elicits inhibitory PSPs in protraction neurons to terminate protraction and excitatory PSPs in retraction neurons to maintain retraction. Pharmacological data indicated that both types of PSPs are mediated by glutamate. Thus, glutamate mediates the dual function of B64 in Aplysia. More generally, our systematic approaches based on RDA may facilitate analyses of transmitter actions in small circuits with identifiable neurons.


Assuntos
Potenciais Pós-Sinápticos Excitadores/fisiologia , Potenciais Pós-Sinápticos Inibidores/fisiologia , Interneurônios/fisiologia , Rede Nervosa/fisiologia , Proteínas Vesiculares de Transporte de Glutamato/fisiologia , Animais , Aplysia , Células COS , Chlorocebus aethiops , Feminino , Masculino , Rede Nervosa/química , Filogenia , Proteínas Vesiculares de Transporte de Glutamato/análise
13.
J Neurophysiol ; 115(3): 1637-43, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26763783

RESUMO

When a behavior is repeated performance often improves, i.e., repetition priming occurs. Although repetition priming is ubiquitous, mediating mechanisms are poorly understood. We address this issue in the feeding network ofAplysia Similar to the priming observed elsewhere, priming inAplysiais stimulus specific, i.e., it can be either "ingestive" or "egestive." Previous studies demonstrated that priming alters motor and premotor activity. Here we sought to determine whether sensorimotor transmission is also modified. We report that changes in sensorimotor transmission do occur. We ask how they are mediated and obtain data that strongly suggest a presynaptic mechanism that involves changes in the "background" intracellular Ca(2+)concentration ([Ca(2+)]i) in primary afferents themselves. This form of plasticity has previously been described and generated interest due to its potentially graded nature. Manipulations that alter the magnitude of the [Ca(2+)]iimpact the efficacy of synaptic transmission. It is, however, unclear how graded control is exerted under physiologically relevant conditions. In the feeding system changes in the background [Ca(2+)]iare mediated by the induction of a nifedipine-sensitive current. We demonstrate that the extent to which this current is induced is altered by peptides (i.e., increased by a peptide released during the repetition priming of ingestive activity and decreased by a peptide released during the repetition priming of egestive activity). We suggest that this constitutes a behaviorally relevant mechanism for the graded control of synaptic transmission via the regulation of the [Ca(2+)]iin a neuron.


Assuntos
Neurônios Motores/fisiologia , Neurônios Aferentes/fisiologia , Priming de Repetição , Transmissão Sináptica , Potenciais de Ação , Animais , Aplysia , Cálcio/metabolismo , Bloqueadores dos Canais de Cálcio/farmacologia , Di-Hidropiridinas/farmacologia , Gânglios dos Invertebrados/efeitos dos fármacos , Gânglios dos Invertebrados/metabolismo , Gânglios dos Invertebrados/fisiologia , Potenciação de Longa Duração , Neurônios Motores/efeitos dos fármacos , Neurônios Motores/metabolismo , Neurônios Aferentes/efeitos dos fármacos , Neurônios Aferentes/metabolismo , Neuropeptídeos/farmacologia , Nifedipino/farmacologia
14.
J Neurophysiol ; 116(4): 1821-1830, 2016 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-27466134

RESUMO

Repetition priming is characterized by increased performance as a behavior is repeated. Although this phenomenon is ubiquitous, mediating mechanisms are poorly understood. We address this issue in a model system, the feeding network of Aplysia This network generates both ingestive and egestive motor programs. Previous data suggest a chemical coding model: ingestive and egestive inputs to the feeding central pattern generator (CPG) release different modulators, which act via different second messengers to prime motor activity in different ways. The ingestive input to the CPG (neuron CBI-2) releases the peptides feeding circuit activating peptide and cerebral peptide 2, which produce an ingestive pattern of activity. The egestive input to the CPG (the esophageal nerve) releases the peptide small cardioactive peptide. This model is based on research that focused on a single aspect of motor control (radula opening). Here we ask whether repetition priming is observed if activity is triggered with a neuron within the core CPG itself and demonstrate that it is not. Moreover, previous studies demonstrated that effects of modulatory neurotransmitters that induce repetition priming persist. This suggests that it should be possible to "prime" motor programs triggered from within the CPG by first stimulating extrinsic modulatory inputs. We demonstrate that programs triggered after ingestive input activation are ingestive and programs triggered after egestive input activation are egestive. We ask where this priming occurs and demonstrate modifications within the CPG itself. This arrangement is likely to have important consequences for "task" switching, i.e., the cessation of one type of motor activity and the initiation of another.


Assuntos
Geradores de Padrão Central/fisiologia , Ingestão de Alimentos/fisiologia , Interneurônios/fisiologia , Atividade Motora/fisiologia , Priming de Repetição/fisiologia , Potenciais de Ação/efeitos dos fármacos , Animais , Aplysia , Geradores de Padrão Central/efeitos dos fármacos , Ingestão de Alimentos/efeitos dos fármacos , Gânglios dos Invertebrados/efeitos dos fármacos , Gânglios dos Invertebrados/fisiologia , Interneurônios/efeitos dos fármacos , Microeletrodos , Modelos Animais , Atividade Motora/efeitos dos fármacos , Neuropeptídeos/administração & dosagem , Neuropeptídeos/metabolismo , Priming de Repetição/efeitos dos fármacos
15.
J Neurosci ; 34(19): 6510-21, 2014 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-24806677

RESUMO

Motor activity is often initiated by a population of command-like interneurons. Command-like interneurons that reliably drive programs have received the most attention, so little is known about how less reliable command-like interneurons may contribute to program generation. We study two electrically coupled interneurons, cerebral-buccal interneuron-2 (CBI-2) and CBI-11, which activate feeding motor programs in the mollusk Aplysia californica. Earlier work indicated that, in rested preparations, CBI-2, a powerful activator of programs, can trigger ingestive and egestive programs. CBI-2 reliably generated ingestive patterns only when it was repeatedly stimulated. The ability of CBI-2 to trigger motor activity has been attributed to the two program-promoting peptides it contains, FCAP and CP2. Here, we show that CBI-11 differs from CBI-2 in that it contains FCAP but not CP2. Furthermore, it is weak in its ability to drive programs. On its own, CBI-11 is therefore less effective as a program activator. When it is successful, however, CBI-11 is an effective specifier of motor activity; that is, it drives mostly ingestive programs. Importantly, we found that CBI-2 and CBI-11 complement each other's actions. First, prestimulation of CBI-2 enhanced the ability of CBI-11 to drive programs. This effect appears to be partly mediated by CP2. Second, coactivation of CBI-11 with CBI-2 makes CBI-2 programs immediately ingestive. This effect may be mediated by specific actions that CBI-11 exerts on pattern-generating interneurons. Therefore, different classes of command-like neurons in a motor network may make distinct, but potentially complementary, contributions as either activators or specifiers of motor activity.


Assuntos
Aplysia/fisiologia , Vias Eferentes/fisiologia , Interneurônios/fisiologia , Atividade Motora/fisiologia , Animais , Bochecha/inervação , Bochecha/fisiologia , Interpretação Estatística de Dados , Ingestão de Alimentos/fisiologia , Fenômenos Eletrofisiológicos/fisiologia , Comportamento Alimentar/fisiologia , Alimentos , Imuno-Histoquímica , Neuropeptídeos/fisiologia , Técnicas de Patch-Clamp
16.
J Neurosci ; 33(1): 93-105, 2013 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-23283325

RESUMO

Although electrical coupling is present in many microcircuits, the extent to which it will determine neuronal firing patterns and network activity remains poorly understood. This is particularly true when the coupling is present in a population of heterogeneous, or intrinsically distinct, circuit elements. We examine this question in the Aplysia californica feeding motor network in five electrically coupled identified cells, B64, B4/5, B70, B51, and a newly identified interneuron B71. These neurons exhibit distinct activity patterns during the radula retraction phase of motor programs. In a subset of motor programs, retraction can be flexibly extended by adding a phase of network activity (hyper-retraction). This is manifested most prominently as an additional burst in the radula closure motoneuron B8. Two neurons that excite B8 (B51 and B71) and one that inhibits it (B70) are active during hyper-retraction. Consistent with their near synchronous firing, B51 and B71 showed one of the strongest coupling ratios in this group of neurons. Nonetheless, by manipulating their activity, we found that B51 preferentially acted as a driver of B64/B71 activity, whereas B71 played a larger role in driving B8 activity. In contrast, B70 was weakly coupled to other neurons and its inhibition of B8 counteracted the excitatory drive to B8. Finally, the distinct firing patterns of the electrically coupled neurons were fine-tuned by their intrinsic properties and the largely chemical cross-inhibition between some of them. Thus, the small microcircuit of the Aplysia feeding network is advantageous in understanding how a population of electrically coupled heterogeneous neurons may fulfill specific network functions.


Assuntos
Potenciais de Ação/fisiologia , Aplysia/fisiologia , Comportamento Alimentar/fisiologia , Rede Nervosa/fisiologia , Neurônios/fisiologia , Animais , Interneurônios/fisiologia , Neurônios Motores/fisiologia
17.
Curr Opin Neurobiol ; 82: 102775, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37625344

RESUMO

The activity of multifunctional networks is configured by neuromodulators that exert persistent effects. This raises a question, does this impact the ability of a network to switch from one type of activity to another? We review studies that have addressed this question in the Aplysia feeding circuit. Task switching in this system occurs "asymmetrically." When there is a switch from egestion to ingestion neuromodulation impedes switching (creates a "negative bias"). When there is a switch from ingestion to egestion the biasing is "positive." Ingestion promotes subsequent egestion. We contrast mechanisms responsible for the two types of biasing and show that the observed asymmetry is a consequence of the fact that there is more than one set of egestive circuit parameters.


Assuntos
Aplysia , Comportamento Alimentar , Animais , Aplysia/fisiologia
18.
Research (Wash D C) ; 6: 0060, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36930762

RESUMO

Locomotion in mollusc Aplysia is implemented by a pedal rolling wave, a type of axial locomotion. Well-studied examples of axial locomotion (pedal waves in Drosophila larvae and body waves in leech, lamprey, and fish) are generated in a segmented nervous system via activation of multiple coupled central pattern generators (CPGs). Pedal waves in molluscs, however, are generated by a single pedal ganglion, and it is unknown whether there are single or multiple CPGs that generate rhythmic activity and phase shifts between different body parts. During locomotion in intact Aplysia, bursting activity in the parapedal commissural nerve (PPCN) was found to occur during tail contraction. A cluster of 20 to 30 P1 root neurons (P1Ns) on the ventral surface of the pedal ganglion, active during the pedal wave, were identified. Computational cluster analysis revealed that there are 2 phases to the motor program: phase I (centered around 168°) and phase II (centered around 357°). PPCN activity occurs during phase II. The majority of P1Ns are motoneurons. Coactive P1Ns tend to be electrically coupled. Two classes of pedal interneurons (PIs) were characterized. Class 1 (PI1 and PI2) is active during phase I. Their axons make a loop within the pedal ganglion and contribute to locomotor pattern generation. They are electrically coupled to P1Ns that fire during phase I. Class 2 (PI3) is active during phase II and innervates the contralateral pedal ganglion. PI3 may contribute to bilateral coordination. Overall, our findings support the idea that Aplysia pedal waves are generated by a single CPG.

19.
J Neurosci ; 31(30): 11039-43, 2011 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-21795552

RESUMO

We study a form of short-term synaptic plasticity that was originally described as a graded potentiating effect of holding potential on spike-mediated synaptic transmission (Shimahara and Tauc, 1975). This form of plasticity has recently generated considerable interest, as it has become apparent that it is present in the mammalian brain (Clark and Häusser, 2006; Marder, 2006). It has been suggested that it adds a previously unappreciated analog component to spike-mediated synaptic transmission (Alle and Geiger, 2006, 2008). A limitation of most previous research in this area is that effects of holding potential have been studied in relative isolation. Presynaptic neurons are stimulated at low frequencies so that a second form of plasticity (homosynaptic facilitation) is not induced. Under physiological conditions, however, both forms of plasticity are likely to be coinduced. In this report, we study the two types of plasticity together in an experimentally advantageous preparation (the mollusk Aplysia californica). Somewhat surprisingly, we find that effects of holding potential can be relatively modest when presynaptic neurons are activated at low frequencies. Interestingly, however, changes in membrane potential are highly effective when homosynaptic facilitation is induced. In this situation, PSPs facilitate at an increased rate. To summarize, our research suggests a novel view of the effect of holding potential on synaptic transmission. We propose that, under physiological conditions, it modifies the dynamics of homosynaptic facilitation.


Assuntos
Fenômenos Biofísicos/fisiologia , Plasticidade Neuronal/fisiologia , Sinapses/fisiologia , Transmissão Sináptica/fisiologia , Potenciais de Ação/fisiologia , Animais , Aplysia , Estimulação Elétrica/métodos , Gânglios dos Invertebrados/citologia , Técnicas In Vitro , Neurônios/fisiologia , Técnicas de Patch-Clamp
20.
J Neurosci ; 31(43): 15438-49, 2011 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-22031890

RESUMO

Complex behaviors often require coordinated movements of dissimilar motor structures. The underlying neural mechanisms are poorly understood. We investigated cycle-by-cycle coordination of two dissimilar feeding structures in Aplysia californica: the external lips and the internal radula. During feeding, the lips open while the radula protracts. Lip and radula motoneurons are located in the cerebral and buccal ganglia, respectively, and radula motoneurons are controlled by a well characterized buccal central pattern generator (CPG). Here, we examined whether the three electrically coupled lip motoneurons C15/16/17 are controlled by the buccal CPG or by a previously postulated cerebral CPG. Two buccal-cerebral projection interneurons, B34 and B63, which are part of the buccal CPG and mediate radula protraction, monosynaptically excite C15/16/17. Recordings from the B34 axon in the cerebral ganglion demonstrate its direct electrical coupling with C15/16/17, eliminating the need for a cerebral CPG. Moreover, when the multifunctional buccal CPG generates multiple forms of motor programs due to the activation of two inputs, the command-like neuron CBI-2 and the esophageal nerve (EN), C15/16 exhibit activity patterns that are distinct from C17. These distinct activity patterns result from combined activity of B34 and B63 and their differential excitation of C15/16 versus C17. In more general terms, we identified neuronal mechanisms that allow a single CPG to coordinate the phasing and activity of remotely located motoneurons innervating distinct structures that participate in the production of different motor outputs. We also demonstrated that axodendritic electrical coupling by projection interneurons plays a pivotal role in coordinating activity of these remotely located neurons.


Assuntos
Axônios/fisiologia , Comportamento Alimentar/fisiologia , Interneurônios/fisiologia , Neurônios Motores/fisiologia , Movimento/fisiologia , Sinapses/fisiologia , Técnicas de Ablação , Animais , Aplysia/fisiologia , Córtex Cerebral/citologia , Estimulação Elétrica/métodos , Eletrofisiologia , Retroalimentação , Lateralidade Funcional/fisiologia , Hidrazinas/metabolismo , Boca/inervação , Vias Neurais/fisiologia , Técnicas de Patch-Clamp/métodos , Potenciais Sinápticos
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